The Albiceleste captain, his country’s all-time record goalscorer, netted a hat-trick in a 7-0 win against Curacao.
Seven-time Ballon d’Or winner Messi hit the 100-mark after he opened the scoring against the Caribbean island Minnows in 20 minutes in Santiago del Estero on Tuesday.
It came 17 years after he opened his Argentina account in a 3-2 defeat to Croatia in March 2006.
The 35-year-old added another goal shortly after the half-hour mark to make it 3-0 and then completed his hat-trick on 37 minutes with the fifth as Argentina toyed with their outclassed opponents.
It was his seventh hat trick for the national team.
“You cannot describe Messi in words,” said fellow goalscorer Nicolas Gonzalez. “He’s the best in the world and he shows it match after match, day after day. Every time he touches the ball, he makes you smile.”
Messi came into the game not just as his country’s all-time record goalscorer, but with more goals than the next two top marksmen – Gabriel Batistuta with 56 and Sergio Aguero with 41 – put together.
This was Argentina’s second match since winning the World Cup in dramatic style against France in Qatar in December – triumphing 4-2 on penalties after a thrilling 3-3 draw – and it was always going to be about Messi reaching 100 goals.
He sits third in the all-time list, behind great rival Cristiano Ronaldo (122) of Portugal and Iran’s Ali Daei (109).